Background: N-farnesyl-norcantharimide (C23H33NO3, designated as NC15) is a norcantharidin derivative with high anti-cancer activity in cell and syngeneic mouse models. However, the anti-cancer mechanism of NC15 is not clear.

Methods: The cell viability of human leukemic Jurkat T (JKT) cells after treatment with NC15 was assessed using cell counting Kit-8 method. The IC50 of NC15-treated JKT cells was estimated using dose–response curve. Flow cytometry analysis, human apoptosis antibody array assay, and whole genome sequencing were performed to investigate the anti-cancer mechanism of NC15 in JKT cells.

Results: The IC50 of NC15 in JKT cells at 24 and 48 h was 2.51 and 2.54 μmol/ml, respectively. The inhibition rates of cell viability were about 80% and 95% when the cells were treated with 8 μmol/ml NC15 for 24 and 48 h, respectively. The percentages of NC15-treated cells in the sub-G1 phase at 24 and 48 h were 22.0% and 34.3 %, respectively, in contrast to the 1.5% in the control. NC15 could not induce apoptosis in JKT cells. Whole genome sequencing of NC15-treated JKT cells showed that many tumor suppressor genes (TSG) were up-regulated, while many genes for steroid biosynthesis, metabolic pathways, and fatty acid metabolism were down-regulated.

Conclusions: The NC15 can reduce the cell viability and increase the percentage of cells in the sub-G1 phase. The NC15 might inhibit progression of JKT cells through the up-regulation of TSG and the down-regulation of steroid biosynthesis, metabolic pathways, and fatty acid metabolism, instead of through apoptosis.